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PHYSIOLOGY OF CARDIAC HYPERTROPHY IN SEVERELY IRON DEFICIENT RATS USING PRESSUREVOLUME LOOPS BY: JACQUIE ZADRA, EMILY THOMPSON , AND ASHLEY WEIGEL FACULT Y MENTOR: BUD CHEW, PH.D. Biology Department Western Wyoming Community College CARDIAC HYPERTROPHY Enlargement of the heart Can either be adaptive or pathological Adaptive hypertrophy is seen in aerobic athletes Pathological hypertrophy is seen in diseases of the heart such as congestive heart failure ADAPTIVE VS PATHOLOGICAL HYPERTROPHY Adaptive hypertrophy Increased cardiac output Increased heart chamber size Healthy heart wall muscle Pathological Hypertrophy Decreased cardiac output No increase in heart chamber size Fibrotic heart wall Due to increase in collagen PROLONGED IRON DEFICIENCY CAUSES CARDIAC HYPERTROPHY CURRENT UNDERSTANDING OF CARDIAC HYPERTROPHY FROM IRON DEFICIENCY 12 weeks of iron deficiency Morphological indications of failure Apoptosis stimulated Cardiac function of this hypertrophy is poorly understood Ref: Dong et al., 2007. HYPOTHESIS We hypothesized that four weeks of iron deficiency would result in failing cardiac function and decreased sympathetic neurotransmitter stores. EXPERIMENTAL DESIGN Two groups Sprague-Dawley Rats Four rats fed iron deficient diet (AIN-93G without iron) Four rats fed control diet (AIN93G) Four weeks of the respective dietary intervention Cardiac pressure-volume loop protocol Plasma and hearts frozen for HPLC analysis PV LOOP PROTOCOL: SURGERY 2 femoral vein catheters for drug infusion 1 jugular vein catheter for saline calibration 1 carotid artery exposure for PV loop transducer Inserted into the carotid artery and passed into the left ventricle PV-LOOP PROTOCOL: DATA COLLECTION Aortic pressure measurements and baseline cardiac function data Inferior Vena Cava occlusion for measure of contractility Saline calibration for parallel conductance subtraction Dopamine infusion Atenolol infusion Second baseline data Heparinized rat to prevent blood clotting Cuvette calibration for measure of true blood volume Collect microhematocrit samples Centrifuge remaining blood for plasma Freeze plasma and hearts for HPLC analysis RESULTS: IRON DEFICIENCY Hematocrit Body Mass *p<0.05 Mass (grams) Hematocrit (Percent) *p<0.05 Group Group RESULTS: CARDIAC HYPERTROPHY Heart•Body Mass-1 Ratio gm•gm-1 *p<0.05 Iron Deficient Control Group PRESSURE-VOLUME LOOPS 150 L V P re s s u re ( m m H g ) 100 End Systolic PV relationship (ESPVR) 50 Isovolumic Relaxation Ejection End Diastolic Volume Stroke Volume Isovolumic Contraction 0 Heart Rate -50 Cardiac output= (SV)(HR) 50 Filling 100 L V Vo lu me ( µL ) 150 RESULTS: PRESSURE-VOLUME LOOPS Control Iron Deficient-Adaptive Iron Deficient-Failing RESULTS: PRESSURE-VOLUME LOOPS Cardiac Output uL•min-1 *p<0.05 Group CO=HR*SV RESULTS: PRESSURE VOLUME LOOPS Heart Rate Stroke Volume 300 250 250 100 150 100 50 0 *p<0.05 200 150 uL bpm 200 50 Control Iron Deficient Group 0 Control Iron Deficient Group RESULTS: PRESSURE VOLUME LOOPS Stroke volume is af fected by three factors: (1) Preload End diastolic volume End Diastolic Volume uL *p<0.05 Group RESULTS: PRESSURE-VOLUME LOOPS (2) Contractility Sympathetic nervous system Ejection fraction Frank-Starling Law of The Heart Ejection Fraction 120 Percent 100 *p<0.05 80 60 40 20 0 Control Iron Deficient Group ESPVR AS A MEASURE OF CONTRACTILIT Y Control rat ejection fraction averaged 55% Iron deficient rat ejection fraction averaged 93% RESULTS: PRESSURE-VOLUME LOOPS mmHg•s-1 dp•dt-1 Max 7000 6000 5000 4000 3000 2000 1000 0 Control Iron Deficient Group RESULTS: PRESSURE-VOLUME LOOPS (3) Afterload Aortic diastolic pressure Pressure (mmHg) Aortic Diastolic Pressure Group PROLONGED IRON DEFICIENCY CAUSES CARDIAC HYPERTROPHY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY HPLC is a technique used to separate and quantify chemical compounds in a liquid medium Used to determine concentration of norepinephrine in extracted plasma RESULTS: HPLC NE (ug•ml-1) Plasma Norepinephrine Concentration 2 1.75 1.5 1.25 1 .75 .5 .25 0 Control Group Iron Deficient CONCLUSION: 3 ADAPTIVE ID HEARTS, 1 FAILING ID HEART ACKNOWLEDGMENTS Thanks to Wyoming INBRE for funding our research